Predicting opioid therapy safety in pancreatic cancer patients

Abstract

Background - Obligatory use of strong opioids for treating chronic pain syndrome in patients with pancreatic cancer provides the implementation of opioid-associated adverse reactions. Genetic and non-genetic risk factors are predictive of the opioid therapy safety. Contemporary methods of information analysis allow using prognostic risk models for practical application. Objective - Identification of significant risk factors for the development of opioid-associated adverse drug reactions in patients with chronic pain syndrome against the background of pancreatic cancer. Material and Methods - The study included 90 patients with chronic pain against the background of pancreatic cancer, randomized at a ratio of 1: 1. Group 1 received morphine sulfate (MS), group 2 received fentanyl transdermal therapeutic system (FTTS) with standard adjuvant therapy (ketoprofen, diazepam, amitriptyline). To assess pain level, the 10-point Digital Rating Scale, the Visual Analogue Scale and the pain questionnaires were used. The assessment of the treatment safety was conducted by the Naranjo Scale. Assessment of prognostic genetic and non-genetic factors was carried out using ROC analysis with calculation of AUC (the area under the ROC-curve). Results - Prognostic models of good quality were determined with the optimal ratio of sensitivity and specificity for the influence of genetic and non-genetic risk factors on the development of opioid-associated adverse drug reactions (OA-ADRs) in comparison groups. Various prognostic factors, complementing each other, were identified in the comparison groups. Conclusion - The following OA-ADRs predicting factors were identified: for FTTS-associated nausea and vomiting - age and carriage of rs7438135 AG genotype of UGT2B7 gene; for local reactions - the sum of points on the ESAS scale and carriage of rs7438135 AA genotype of UGT2B7 gene; for difficulty urinating - the level of glomerular filtration rate; for neurotoxicity - the level of AST and bilirubin, and the carriage of rs1128503 GG genotype of ABCB1 gene; for pruritus - carriage of rs1045642642 AA genotype of ABCB1 gene. The prognostic factors for the implementation of MS-associated neurotoxicity were age and comorbidity; for dry mouth was predicted best from the sum of points on the MMCE scale; weakness was predicted by the carriage of rs7668258 TT genotype of UGT2B7 gene.